(Circulation. 1997;96:1906-1913.)
© 1997 American Heart Association, Inc.
Articles |
Stimulated Activation of Platelet-Derived Growth Factor Receptor In Vivo in Balloon-Injured Arteries
A Link Between Angiotensin II and Intimal Thickening
From the Departments of Cardiovascular Biology (J.A., M.N., Y.T.), Surgery (J.D., M.M.), Internal Medicine (M.O., K.K.), and Physiology (N.T.), Faculty of Medicine, University of Tokyo, and the Department of Pathology, National Cancer Center East Hospital, Kashiwa, and Department of Laboratory Medicine (T.M.), Mitsui Memorial Hospital, Tokyo, Japan.
Correspondence to Yoh Takuwa, MD, Department of Cardiovascular Biology, Faculty of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.
Background Growth factors such as platelet-derived growth factor (PDGF) have been postulated to be important mediators of neointimal formation in balloon-injured artery. Binding of growth factors to their receptors activates intrinsic receptor tyrosine kinase, resulting in tyrosine phosphorylation of receptors themselves and cellular substrate proteins. We investigated in vivo activities of growth factors by determining the extent of tyrosine phosphorylation of growth factor receptors and substrate proteins in injured artery.
Methods and Results Rat balloon-injured carotid artery was
analyzed for phosphotyrosine content of PDGF 
- and
ß-receptors, epidermal growth factor (EGF) receptors, and insulin
receptor substrate-1 (IRS-1) by immunoprecipitation and
anti-phosphotyrosine Western blot. The development of intimal
thickening after deendothelializing balloon
catheterization of rat carotid artery was accompanied
by transient twofold to threefold increases in the extent of tyrosyl
phosphorylation of PDGF - and ß-receptors but not
EGF receptor or IRS-1. The AT1 angiotensin II
(Ang II) receptor antagonist TCV-116 markedly inhibited
both tyrosyl phosphorylation of PDGF - and
ß-receptors and intimal thickening. The AT1
antagonist reduced mRNA levels of both PDGF-A and -B chains
in injured arteries.
Conclusions The present study provides direct evidence for increased PDGF activities in injured artery in situ and the involvement of Ang II in stimulated activation of PDGF receptors. These results are consistent with the pathogenetic role for PDGF in intimal thickening.
Key Words: stenosis • growth substances • balloon
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